This program project in Clinical Cancer Research is this Institutions's major effort in translational research. New drugs and biologicals are assessed from (I) the laboratories of the Sloan-Kettering Institute and from extra-mural scientists with whom the Center has active collaboration, (2) the drug development program of the National Cancer Institute, and (3) the pharmaceutical industry. Ideas and concepts (new drugs, new use of drugs and integration of other modalities in cancer treatment) are tested in Phase I trials in Project I, and studied further in Project II (hematologic malignancies) and in Project III (solid tumors). The general themes that are explored in this proposal are (1) the value of second generation differentiating agents in the treatment of malignancies (e.g., retinoids, HMBA analogs), (2) dose intensification in the treatment of both hematologic malignancies and certain solid tumors, (3) biochemical modulation and combination chemotherapy, and (4) the integration of other modalities (radiation therapy and antibody treatment) with chemotherapy to treat malignant disease. This program is facilitated by these Cores: a Biostatistics Core, that provides biostatistic input into protocol design and outcome analysis, and a Pharmacology Core, that provides analytical support to the projects.